Sensor arrays for detecting analytes in fluids

ABSTRACT

Chemical sensors for detecting analytes in fluids comprise first and second conductive elements (e.g. electrical leads) electrically coupled to and separated by a chemically sensitive resistor which provides an electrical path between the conductive elements. The resistor comprises a plurality of alternating nonconductive regions (comprising a nonconductive organic polymer) and conductive regions (comprising a conductive material) transverse to the electrical path. The resistor provides a difference in resistance between the conductive elements when contacted with a fluid comprising a chemical analyte at a first concentration, than when contacted with a fluid comprising the chemical analyte at a second different concentration. Arrays of such sensors are constructed with at least two sensors having different chemically sensitive resistors providing dissimilar such differences in resistance. Variability in chemical sensitivity from sensor to sensor is provided by qualitatively or quantitatively varying the composition of the conductive and/or nonconductive regions. An electronic nose for detecting an analyte in a fluid may be constructed by using such arrays in conjunction with an electrical measuring device electrically connected to the conductive elements of each sensor.

[0001] The research carried out in the subject application was supportedin part by grants from the National Science Foundation (CHE 9202583).The government may have rights in any patent issuing on thisapplication.

INTRODUCTION

[0002] 1. Field of the Invention

[0003] The field of the invention is electrical sensors for detectinganalytes in fluids.

[0004] 2. Background

[0005] There is considerable interest in developing sensors that act asanalogs of the mammalian olfactory system (1-2). This system is thoughtto utilize probabilistic repertoires of many different receptors torecognize a single odorant (3-4). In such a configuration, the burden ofrecognition is not on highly specific receptors, as in the traditional“lock-and-key” molecular recognition approach to chemical sensing, butlies instead on the distributed pattern processing of the olfactory bulband the brain (5-6).

[0006] Prior attempts to produce a broadly responsive sensor array haveexploited heated metal oxide thin film resistors (7-9), polymer sorptionlayers on the surfaces of acoustic wave resonators (10-11), arrays ofelectrochemical detectors (12-14), or conductive polymers (15-16).Arrays of metal oxide thin film resistors, typically based on SnO₂ filmsthat have been coated with various catalysts, yield distinct, diagnosticresponses for several vapors (7-9). However, due to the lack ofunderstanding of catalyst function, SnO₂ arrays do not allow deliberatechemical control of the response of elements in the arrays norreproducibility of response from array to array. Surface acoustic waveresonators are extremely sensitive to both mass and acoustic impedancechanges of the coatings in array elements, but the signal transductionmechanism involves somewhat complicated electronics, requiring frequencymeasurement to 1 Hz while sustaining a 100 MHz Rayleigh wave in thecrystal (10-11). Attempts have been made to construct sensors withconducting polymer elements that have been grown electrochemicallythrough nominally identical polymer films and coatings (15-18). It is anobject herein to provide a broadly responsive analyte detection sensorarray based on a variety of “chemisresistor” elements. Such elements aresimply prepared and are readily modified chemically to respond to abroad range of analytes. In addition, these sensors yield a rapid, lowpower, dc electrical signal in response to the fluid of interest, andtheir signals are readily integrated with software or hardware-basedneural networks for purposes of analyte identification.

RELEVANT LITERATURE

[0007] Pearce et al (1993) Analyst 118, 371-377 and Gardner et al (1994)Sensors and Actuators B, 18-19, 240-243 describe polypyrrole-basedsensor arrays for monitoring beer flavor. Shurmer (1990) U.S. Pat. No.4,907,441 describes general sensor arrays with particular electricalcircuitry.

SUMMARY OF THE INVENTION

[0008] The invention provides methods, apparatuses and expert systemsfor detecting analytes in fluids. The apparatuses include a chemicalsensor comprising first and second conductive elements (e.g. electricalleads) electrically coupled to a chemically sensitive resistor whichprovides an electrical path between the conductive elements. Theresistor comprises a plurality of alternating nonconductive regions(comprising a nonconductive organic polymer) and conductive regions(comprising a conductive material). The electrical path between thefirst and second conductive elements is transverse to (i.e. passesthrough) said plurality of alternating nonconductive and conductiveregions. In use, the resistor provides a difference in resistancebetween the conductive elements when contacted with a fluid comprising achemical analyte at a first concentration, than when contacted with afluid comprising the chemical analyte at a second differentconcentration. The electrical path through any given nonconductiveregion is typically on the order of 100 angstroms in length, providing aresistance of on the order of 100 mΩ across the region. Variability inchemical sensitivity from sensor to sensor is conveniently provided byqualitatively or quantitatively varying the composition of theconductive and/or nonconductive regions. For example, in one embodiment,the conductive material in each resistor is held constant (e.g. the sameconductive material such as polypyrrole) while the nonconductive organicpolymer varies between resistors (e.g. different plastics such aspolystyrene).

[0009] Arrays of such sensors are constructed with at least two sensorshaving different chemically sensitive resistors providing dissimilardifferences in resistance. An electronic nose for detecting an analytein a fluid may be constructed by using such arrays in conjunction withan electrical measuring device electrically connected to the conductiveelements of each sensor. Such electronic noses may incorporate a varietyof additional components including means for monitoring the temporalresponse of each sensor, assembling and analyzing sensor data todetermine analyte identity, etc. Methods of making and using thedisclosed sensors, arrays and electronic noses are also provided.

BRIEF DESCRIPTION OF THE FIGURES

[0010]FIG. 1(A) shows an overview of sensor design; FIG. 1(B) shows anoverview of sensor operation; FIG. 1(C) shows an overview of systemoperation.

[0011]FIG. 2. Cyclic voltammogram of a poly(pyrrole)-coated platinumelectrode. The electrolyte was 0.10 M [(C₄H₉)₄N]⁺[ClO₄]⁻ inacetonitrile, with a scan rate of 0.10 V s⁻¹.

[0012]FIG. 3(A) shows the optical spectrum of a spin coatedpoly(pyrrole) film that had been washed with methanol to remove excesspyrrole and reduced phosphomolybdic acid. FIG. 3(B) shows the opticalspectrum of a spin-coated poly(pyrrole) film on indium-tin-oxide after10 potential cycles between +0.70 and −1.00 V vs. SCE in 0.10 M[(C₄H₉)₄N]⁺[ClO₄]⁻ in acetonitrile at a scan rate of 0.10 V-s⁻¹. Thespectra were obtained in 0.10 M KCl—H₂O.

[0013]FIG. 4(A) Schematic of a sensor array showing an enlargement ofone of the modified ceramic capacitors used as sensing elements. Theresponse patterns generated by the sensor array described in Table 3 aredisplayed for: FIG. 4(B) acetone; FIG. 4(C) benzene; and FIG. 4(D)ethanol.

[0014] FIGS. 5(A)-(D). Principle component analysis of autoscaled datafrom individual sensors containing different plasticizers: (A)poly(styrene); (B) poly (α-methyl styrene); (C)poly(styrene-acrylonitrile); (D) poly(styrene-allyl alcohol).

[0015] FIGS. 6(A) & 6(B). Principle component analysis of data obtainedfrom all sensors (Table 3). Conditions and symbols are identical toFIGS. 5(A)-(D). FIG. 6A shows data represented in the first threeprinciple components pc1, pc2 and pc3, while FIG. 6B shows the data whenrepresented in pc1, pc2, and pc4. A higher degree of discriminationbetween some solvents could be obtained by considering the fourthprinciple component as illustrated by larger separations betweenchloroform, tetrahydrofuran, and isopropyl alcohol in FIG. 6B.

[0016]FIG. 7(A). Plot of acetone partial pressure (O) as a function ofthe first principle component; linear least square fit (−) between thepartial pressure of acetone and the first principle component(P_(a)=8.26·pc1+83.4, R²=0.989); acetone partial pressure (+) predictedfrom a multi-linear least square fit between the partial pressure ofacetone and the first three principle components(P_(a)=8.26·pc1−0.673·pc2+6.25·pc3+83.4, R²=0.998). FIG. 7(B). Plot ofthe mole fraction of methanol, x_(m), (O) in a methanol-ethanol mixtureas a function of the first principle component; linear least square fit( - - - ) between X_(m) and the first principle component(x_(m)=0.112*·pc1+0.524, R²=0.979); x_(m) predicted from a multi-linearleast square fit (+) between x_(m) and the first three principlecomponents (x_(m)=0.112·pc1−0.0300·pc2−0.0444·pc3+0.524, R²=0.987).

[0017]FIG. 8. The resistance response of apoly(N-vinylpyrrolidone):carbon black (20 w/w % carbon black) sensorelement to methanol, acetone, and benzene. The analyte was introduced att=60 s for 60 s. Each trace is normalized by the resisance of the sensorelement (approx. 125 Ω) before each exposure.

[0018]FIG. 9. First three principal components for the response of acarbon-black based sensor array with 10 element. The non-conductivecomponents of the carbon-black composites used are listed in Table 3,and the resistors were 20 w/w % carbon black.

DETAILED DESCRIPTION OF THE INVENTION

[0019] The invention provides sensor arrays for detecting an analyte ina fluid for use in conjunction with an electrical measuring apparatus.These arrays comprise a plurality of compositionally different chemicalsensors. Each sensor comprises at least first and second conductiveleads electrically coupled to and separated by a chemically sensitiveresistor. The leads may be any convenient conductive material, usually ametal, and may be interdigitized to maximize signal-to-noise strength.

[0020] The resistor comprises a plurality of alternating nonconductiveand conductive regions transverse to the electrical path between theconductive leads. Generally, the resistors are fabricated by blending aconductive material with a nonconductive organic polymer such that theelectrically conductive path between the leads coupled to the resistoris interrupted by gaps of non-conductive organic polymer material. Forexample, in a colloid, suspension or dispersion of particulateconductive material in a matrix of nonconductive organic polymermaterial, the matrix regions separating the particles provide the gaps.The nonconductive gaps range in path length from about 10 to 1,000angstroms, usually on the order of 100 angstroms providing individualresistance of about 10 to 1,000 mΩ, usually on the order of 100 m Ω,across each gap. The path length and resistance of a given gap is notconstant but rather is believed to change as the nonconductive organicpolymer of the region absorbs, adsorbs or imbibes an analyte.Accordingly the dynamic aggregate resistance provided by these gaps in agiven resistor is a function of analyte permeation of the nonconductiveregions. In some embodiments, the conductive material may alsocontribute to the dynamic aggregate resistance as a function of analytepermeation (e.g. when the conductive material is a conductive organicpolymer such as polyprryole).

[0021] A wide variety of conductive materials and nonconductive organicpolymer materials can be used. Table 1 provides exemplary conductivematerials for use in resistor fabrication; mixtures, such as of thoselisted, may also be used. Table 2 provides exemplary nonconductiveorganic polymer materials; blends and copolymers, such as of thepolymers listed here, may also be used Combinations, concentrations,blend stoichiometries, percolation thresholds, etc. are readilydetermined empirically by fabricating and screening prototype resistors(chemiresistors) as described below. TABLE 1 Major Class ExamplesOrganic conducting polymers (poly(anilines), Conductorspoly(thiophenes), poly(pyrroles), poly(acetylenes), etc.)), carbonaceousmaterials (carbon blacks, graphite, coke, C₆₀, etc.), charge transfercomplexes (tetramethylparaphenylenediamine-chloranile, alkali metaltetracyanoquinodimethane complexes, tetrathiofulvalene halide complexes,etc.), etc. Inorganic metals and metal alloys (Ag, Au, Cu, Pt, AuCuConductors alloy, etc.), highly doped semiconductors (Si, GaAs InP,MoS₂, TiO₂, etc.), conductive metal oxides (In₂O₃, SnO₂, Na_(x)Pt₃O₄,etc.), superconductors (YBa₂Cu₃O₇, Tl₂Ba₂Ca₂Cu₃O₁₀, etc.), etc. Mixedinorganic/ Tetracyanoplatinate complexes, Iridium halocarbony organiccomplexes, stacked macrocyclic complexes, etc. Conductors

[0022] TABLE 2 Major Class Examples Main-chain poly(dienes),poly(alkenes), poly(acrylics), carbon poly(methacrylics), poly(vinylethers), poly(vinyl polymers thioethers), poly(vinyl alcohols),poly(vinyl ketones), poly(vinyl halides), poly(vinyl nitriles),poly(vinyl esters), poly(styrenes), poly(arylenes), etc. Main-chainpoly(oxides), poly(carbonates), poly(esters), acyclic poly(anhydrides),poly(urethanes), poly(sulfonates), heteroatom poly(siloxanes),poly(sulfides), poly(thioesters), polymers poly(sulfones),poly(sulfonamides), poly(amides), poly(ureas), poly(phosphazenes),poly(silanes), poly(silazanes), etc. Main-chain poly(furantetracarboxylic acid diimides), heterocyclic poly(benzoxazoles),poly(oxadiazoles), polymers poly(benzothiazinophenothiazines),poly(benzothiazoles poly(pyrazinoquinoxalines), poly(pyromellitimides),poly(quinoxalines), poly(benzimidazoles), poly(oxindoles),poly(oxoisoindolines), poly(dioxoisoindolines), poly(triazines),poly(pyridazines), poly(piperazines), poly(pyridines), poly(piperidines), poly(triazoles), poly(pyrazoles), poly(pyrrolidines),poly(carboranes), poly (oxabicyclononanes), poly(dibenzofurans),poly(phthalides), poly(acetals), poly(anhydrides), carbohydrates, etc.

[0023] The chemiresistors can be fabricated by many techniques such as,but not limited to, solution casting, suspension casting, and mechanicalmixing. In general, solution cast routes are advantageous because theyprovide homogeneous structures and ease of processing. With solutioncast routes, resistor elements may be easily fabricated by spin, sprayor dip coating. Since all elements of the resistor must be soluble,however, solution cast routes are somewhat limited in theirapplicability. Suspension casting still provides the possibility ofspin, spray or dip coating but more heterogeneous structures than withsolution casting are expected. With mechanical mixing, there are nosolubility restrictions since it involves only the physical mixing ofthe resistor components, but device fabrication is more difficult sincespin, spray and dip coating are no longer possible. A more detaileddiscussion of each of these follows.

[0024] For systems where both the conducting and non-conducting media ortheir reaction precursors are soluble in a common solvent, thechemiresistors can be fabricated by solution casting. The oxidation ofpyrrole by phosphomolybdic acid presented herein represents such asystem. In this reaction, the phosphomolybdic acid and pyrrole aredissolved in THF and polymerization occurs upon solvent evaporation.This allows for THF soluble non-conductive polymers to be dissolved intothis reaction mixture thereby allowing the blend to be formed in asingle step upon solvent evaporation. The choice of non-conductivepolymers in this route is, of course, limited to those that are solublein the reaction media. For the poly(pyrrole) case described above,preliminary reactions were performed in THF, but this reaction should begeneralizable to other non-aqueous solvent such as acetonitrile orether. A variety of permutations on this scheme are possible for otherconducting polymers. Some of these are listed below. Certain conductingpolymers, such as substituted poly(cyclooctatetraenes), are soluble intheir undoped, non-conducting state in solvents such as THF oracetonitrile. Consequently, the blends between the undoped polymer andplasticizing polymer can be formed from solution casting. After which,the doping procedure (exposure to I₂vapor, for instance) can beperformed on the blend to render the substituted poly(cyclooctatetraene)conductive. Again, the choice of non-conductive polymers is limited tothose that are soluble in the solvents that the undoped conductingpolymer is soluble in and to those stable to the doping reaction.Certain conducting polymers can also be synthesized via a solubleprecursor polymer. In these cases, blends between the precursor polymerand the non-conducting polymer can first be formed followed by chemicalreaction to convert the precursor polymer into the desired conductingpolymer. For instance poly(p-phenylene vinylene) can be synthesizedthrough a soluble sulfonium precursor. Blends between this sulfoniumprecursor and the non-conductive polymer can be formed by solutioncasting. After which, the blend can be subjected to thermal treatmentunder vacuum to convert the sulfonium precursor to the desiredpoly(p-phenylene vinylene).

[0025] In suspension casting, one or more of the components of theresistor is suspended and the others dissolved in a common solvent.Suspension casting is a rather general technique applicable to a widerange of species, such as carbon blacks or colloidal metals, which canbe suspended in solvents by vigorous mixing or sonication. In oneapplication of suspension casting, the non-conductive polymer isdissolved in an appropriate solvent (such as THF, acetonitrile, water,etc.). Colloidal silver is then suspended in this solution and theresulting mixture is used to dip coat electrodes.

[0026] Mechanical mixing is suitable for all of theconductive/non-conductive combinations possible. In this technique, thematerials are physically-mixed in a ball-mill or other mixing device.For instance, carbon black: non-conductive polymer composites arereadily made by ball-milling. When the non-conductive polymer can bemelted or significantly softened without decomposition, mechanicalmixing at elevated temperature can improve the mixing process.Alternatively, composite fabrication can sometimes be improved byseveral sequential heat and mix steps.

[0027] Once fabricated, the individual elements can be optimized for aparticular application by varying their chemical make up andmorphologies. The chemical nature of the resistors determines to whichanalytes they will respond and their ability to distinguish differentanalytes. The relative ratio of conductive to insulating componentsdetermines the magnitude of the response since the resistance of theelements becomes more sensitive to sorbed molecules as the percolationthreshold is approached. The film morphology is also important indetermining response characteristics. For instance, thin films respondmore quickly to analytes than do thick ones. Hence, with an empiricalcatalogue of information on chemically diverse sensors made with varyingratios of insulating to conducting components and by differingfabrication routes, sensors can be chosen that are appropriate for theanalytes expected in a particular application, their concentrations, andthe desired response times. Further optimization can then be performedin an iterative fashion as feedback on the performance of an array underparticular conditions becomes available.

[0028] The resistor may itself form a substrate for attaching the leador the resistor. For example, the structural rigidity of the resistorsmay be enhanced through a variety of techniques:chemical or radiationcross-linking of polymer components (dicumyl peroxide radicalcross-linking, UV-radiation cross-linking of poly(olefins), sulfurcross-linking of rubbers, e-beam cross-linking of Nylon, etc.), theincorporation of polymers or other materials into the resistors toenhance physical properties (for instance, the incorporation of a highmolecular weight, high Tm polymers), the incorporation of the resistorelements into supporting matrices such as clays or polymer networks(forming the resistor blends within poly-(methylmethacrylate) networksor within the lamellae of montmorillonite, for instance), etc. Inanother embodiment, the resistor is deposited as a surface layer on asolid matrix which provides means for supporting the leads. Typically,the matrix is a chemically inert, non-conductive substrate such as aglass or ceramic.

[0029] Sensor arrays particularly well-suited to scaled up productionare fabricated using IC design technologies. For example, thechemiresistors can easily be integrated onto the front end of a simpleamplifier interfaced to an A/D converter to efficiently feed the datastream directly into a neural network software or hardware analysissection. Micro-fabrication techniques can integrate the chemiresistorsdirectly onto a micro-chip which contains the circuitry for analoguesignal conditioning/processing and then data analysis. This provides forthe production of millions of incrementally different sensor elements ina single manufacturing step using ink-jet technology. Controlledcompositional gradients in the chemiresistor elements of a sensor arraycan be induced in a method analogous to how a color ink-jet printerdeposits and mixes multiple colors. However, in this case rather thanmultiple colors, a plurality of different polymers in solution which canbe deposited are used A sensor array of a million distinct elements onlyrequires a 1 cm×1 cm sized chip employing lithography at the 10 μmfeature level, which is within the capacity of conventional commercialprocessing and deposition methods. This technology permits theproduction of sensitive, small-sized, stand-alone chemical sensors.

[0030] Preferred sensor arrays have a predetermined inter-sensorvariation in the structure or composition of the nonconductive organicpolymer regions. The variation may be quantitative and/or qualitative.For example, the concentration of the nonconductive organic polymer inthe blend can be varied across sensors. Alternatively, a variety ofdifferent organic polymers may be used in different sensors. Anelectronic nose for detecting an analyte in a fluid is fabricated byelectrically coupling the sensor leads of an array of compositionallydifferent sensors to an electrical measuring device. The device measureschanges in resistivity at each sensor of the array, preferablysimultaneously and preferably over time. Frequently, the device includessignal processing means and is used in conjunction with a computer anddata structure for comparing a given response profile to astructure-response profile database for qualitative and quantitativeanalysis. Typically such a nose comprises at least ten, usually at least100, and often at least 1000 different sensors though with massdeposition fabrication techniques described herein or otherwise known inthe art, arrays of on the order of at least 10⁶ sensors are readilyproduced.

[0031] In operation, each resistor provides a first electricalresistance between its conductive leads when the resistor is contactedwith a first fluid comprising a chemical analyte at a firstconcentration, and a second electrical resistance between its conductiveleads when the resistor is contacted with a second fluid comprising thesame chemical analyte at a second different concentration. The fluidsmay be liquid or gaseous in nature. The first and second fluids mayreflect samples from two different environments, a change in theconcentration of an analyte in a fluid sampled at two time points, asample and a negative control, etc. The sensor array necessarilycomprises sensors which respond differently to a change in an analyteconcentration, i.e. the difference between the first and secondelectrical resistance of one sensor is different from the differencebetween the first second electrical resistance of another sensor.

[0032] In a preferred embodiment, the temporal response of each sensor(resistance as a function of time) is recorded. The temporal response ofeach sensor may be normalized to a maximum percent increase and percentdecrease in resistance which produces a response pattern associated withthe exposure of the analyte. By iterative profiling of known analytes, astructure-function database correlating analytes and response profilesis generated. Unknown analyte may then be characterized or identifiedusing response pattern comparison and recognition algorithms.Accordingly, analyte detection systems comprising sensor arrays, anelectrical measuring devise for detecting resistance across eachchemiresistor, a computer, a data structure of sensor array responseprofiles, and a comparison algorithm are provided. In anotherembodiment, the electrical measuring device is an integrated cicuitcomprising neural network-based hardware and a digital-analog convertermultiplexed to each sensor, or a plurality of DACs, each connected todifferent sensor(s).

[0033] A wide variety of analytes and fluids may be analyzed by thedisclosed sensors, arrays and noses so long as the subject analyte iscapable generating a differential response across a plurality of sensorsof the array. Analyte applications include broad ranges of chemicalclasses such as organics such as alkanes, alkenes, alkynes, dienes,alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes,carbonyls, carbanions, polynuclear aromatics and derivatives of suchorganics, e.g. halide derivatives, etc., biomolecules such as sugars,isoprenes and isoprenoids, fatty acids and derivatives, etc.Accordingly, commercial applications of the sensors, arrays and nosesinclude environmental toxicology and remediation, biomedicine, materialsquality control, food and agricultural products monitoring, etc.

[0034] The general method for using the disclosed sensors, arrays andelectronic noses, for detecting the presence of an analyte in a fluidinvolves resistively sensing the presence of an analyte in a fluid witha chemical sensor comprising first and second conductive leadselectrically coupled to and separated by a chemically sensitive resistoras described above by measuring a first resistance between theconductive leads when the resistor is contacted with a first fluidcomprising an analyte at a first concentration and a second differentresistance when the resistor is contacted with a second fluid comprisingthe analyte at a second different concentration. The following examplesare offered by way of illustration and not by way of limitation.

EXAMPLES

[0035] Polymer Synthesis. Poly(pyrrole) films used for conductivity,electrochemical, and optical measurements were prepared by injectingequal volumes of N₂-purged solutions of pyrrole (1.50 mmoles in 4.0 mldry tetrahydrofuran) and phosphomolybdic acid (0.75 mmoles in 4.0 mltetrahydrofuran) into a N₂-purged test tube. Once the two solutions weremixed, the yellow phosphomolybdic acid solution turned dark green, withno observable precipitation for several hours. This solution was usedfor film preparation within an hour of mixing.

[0036] Sensor Fabrication. Plasticized poly(pyrrole) sensors were madeby mixing two solutions, one of which contained 0.29 mmoles pyrrole in5.0 ml tetrahydrofuran, with the other containing 0.25 mmolesphosphomolybdic acid and 30 mg of plasticizer in 5.0 ml oftetrahydrofuran. The mixture of these-two solutions resulted in a w:wratio of pyrrole to plasticizer of 2:3. An inexpensive, quick method forcrating the chemiresistor array elements was accomplished by effecting across sectional cut through commercial 22 nF ceramic capacitors (KemetElectronics Corporation). Mechanical slices through these capacitorsrevealed a series of interdigitated metal lines (25% Ag:75% Pt),separated by 15 μm, that could be readily coated with conductingpolymer. The monomer-plasticizer-oxidant solutions were then used to dipcoat interdigitated electrodes in order to provide a robust electricalcontact to the polymerized organic films. After polymerization wascomplete, the film was insoluble and was rinsed with solvent(tetrahydrofuran or methanol) to remove residual phosphomolybdic acidand unreacted monomer. The sensors were then connected to a commercialbus strip, with the resistances of the various “chemiresistor” elementsreadily monitored by use of a multiplexing digital ohmmeter.

[0037] Instrumentation. Optical spectra were obtained on a HewlettPackard 8452A spectrophotometer, interfaced to an IBM XT.Electrochemical experiments were performed using a Princeton AppliedResearch Inc. 173 potentiostat/175 universal programmer. Allelectrochemical experiments were performed with a Pt flag auxiliary anda saturated calomel reference electrode (SCE). Spin-coating wasperformed on a Headway Research Inc. photoresist spin coater. Filmthicknesses were determined with a Dektak Model 3030 profilometer.Conductivity measurements were performed with an osmium-tipped fourpoint probe (Alessi Instruments Inc., tip spacing=0.050″, tipradii=0.010″). Transient resistance measurements were made with aconventional multimeter (Fluke Inc., “Hydra Data Logger” Meter).

[0038] Principle Component Analysis and Multi-linear Least Square Fits.A data set obtained from a single exposure of the array to an odorantproduced a set of descriptors (i.e. resistances), d_(i). The dataobtained from multiple exposures thus produced a data matrix D whereeach row, designated by j, consisted of n descriptors describing asingle member of the data set (i.e. a single exposure to an odor). Sincethe baseline resistance and the relative changes in resistance variedamong sensor,s the data matrix was autoscaled before further processing(19). In this preprocessing technique, all the data associated with asingle descriptor (i.e. a column in the data matrix) were centeredaround zero with unit standard deviation

d′ _(ij)=(d _(ij) −{overscore (d)} _(i))/σ_(i)  (1)

[0039] where {overscore (d)}_(i) is the mean value for descriptor i andσ_(i) is the corresponding standard deviation.

[0040] Principle component analysis (19) was performed to determinelinear combinations of the data such that the maximum variance [definedas the square of the standard deviation] between the members of the dataset was obtained in n mutually orthogonal dimensions. The linearcombinations of the data resulted in the largest variance [orseparation] between the members of the data set in the first principlecomponent (pc1) and produced decreasing magnitudes of variance from thesecond to the n^(th) principle component (pc2−pcn). The coefficientsrequired to transform the autoscaled data into principle component space(by-linear combination) were determined by multiplying the data matrix,D, by its transpose, D^(T) (i.e. diagnolizing the matrix) (19)

R=D ^(T) ·D  (2)

[0041] This operation produced the correlation matrix, R whose diagonalelements were unity and whose off-diagonal elements were the correlationcoefficients of the data. The total variance in the data was thus givenby the sum of the diagonal elements in R. The n eigenvalues, and thecorresponding n eigenvectors, were then determined for R. Eacheigenvector contained a set of n coefficients which were used totransform the data by linear combination into one of its n principlecomponents. The corresponding eigenvalue yielded the fraction of thetotal variance that was contained in that principle component. Thisoperation produced a principle component matrix, P, which had the samedimensions as the original data matrix. Under these conditions, each rowof the matrix P was still associated with a particular odor and eachcolumn was associated with a particular principle component.

[0042] Since the values in the principle component space had no physicalmeaning, it was useful to express the results of the principle componentanalysis in terms of physical parameters such as partial pressure andmole fraction. This was achieved via a multi-linear least square fitbetween the principle component values and the corresponding parameterof interest. A multi-linear least square fit resulted in a linearcombination of the principle components which yielded the best fit tothe corresponding parameter value. Fits were achieved by appending acolumn with each entry being unity to the principle component matrix P,with each row, j, corresponding to a different parameter value (e.g.partial pressure), v_(j), contained in vector V. The coefficients forthe best multi-linear fit between the principle components and parameterof interest were obtained by the following matrix operation

C=(P ^(T) ·P)⁻¹ ·P ^(T) ·V  (3)

[0043] where C was a vector containing the coefficients for the linearcombination.

[0044] A key to our ability to fabricate chemically diverse sensingelements was the preparation of processable, air stable films ofelectrically conducting organic polymers. This was achieved through thecontrolled chemical oxidation of pyrrole (PY) using phosphomolybdic acid(H₃PMo₁₂O₄₀) (20 in tetrahydrofuran:

PY→PY*⁺+e⁻  (4)

2PY*⁺→PY₂+2H⁺  (5)

H₃PMo₁₂O₄₀+2e⁻+2H⁺→H₅PMo₁₂O₄₀  (6)

[0045] The redox-driven or electrochemically-induced polymerization ofpyrrole has been explored previously, but this process typically yieldsinsoluble, intractable deposits of poly(pyrrole) as the product (21).Our approach was to use low concentrations of the H₃PMo₁₂O₄₀ oxidant(E°=+0.36 V vs. SCE) (20). Since the electrochemical potential ofPY⁺*/PY is more positive (E°=+1.30 V vs. SCE) (22) than that ofH₃PMo₁₂O₄₀/H₅PMo₁₂O₄₀, the equilibrium concentration of PY⁺*, and thusthe rate of polymerization, was relatively low in dilute solutions (0.19M PY, 0.09 M H₃PMo₁₂O₄₀). However, it has been shown that the oxidationpotential of pyrrole oligomers decreases from +1.20 V to +0.55 to +0.26V vs. SCE as the number of units increase from one to two to three, andthat the oxidation potential of bulk poly(pyrrole) occurs at −0.10 V vs.SCE (23). As a result, oxidation of pyrrole trimers by phosphomolybdicacid is expected to be thermodynamically favorable. This allowedprocessing of the monomer-oxidant solution (i.e. spin coating, dipcoating, introduction of plasticizers, etc.), after which timepolymerization to form thin films was simply effected by evaporation ofthe solvent. The dc electrical conductivity of poly(pyrrole) filmsformed by this method on glass slides, after rinsing the films withmethanol to remove excess phosphomolybdic acid and/or monomer, was onthe order of 15-30 S-cm⁻¹ for films ranging from 40-100 nm in thickness.

[0046] The poly(pyrrole) films produced in this work exhibited excellentelectrochemical and optical properties. For example, FIG. 2 shows thecyclic voltammettic behavior of a chemically polymerized poly(pyrrole)film following ten cycles from −1.00 V to +0.70 V vs. SCE. The cathodicwave at −0.40 V corresponded to the reduction of poly(pyrrole) to itsneutral, nonconducting state, and the anodic wave at −0.20 Vcorresponded to the reoxidation of poly(pyrrole) to its conducting state(24). The lack of additional faradaic current, which would result fromthe oxidation and reduction of phosphomolybdic acid in the film,suggests that the Keggin structure of phosphomolybdic acid was notpresent in the film anions (25) and implies that MoO₄ ²⁻, or otheranions, served as the poly(pyrrole) counterions in the polymerizedfilms.

[0047]FIG. 3A shows the optical spectrum of a processed polypyrrole filmthat had been spin-coated on glass-and then rinsed with methanol. Thesingle absorption maximum was characteristic of a highly oxidizedpoly(pyrrole) (26), and the absorption band at 4.0 eV was characteristicof an interband transition between the conduction and valence bands. Thelack of other bands in this energy range was evidence for the presenceof bipolaron states (see FIG. 3A), as have been observed in highlyoxidized poly(pyrrole) (26). By cycling the film in 0.10 M[(C₄H₉)₄N]⁺[ClO₄]⁻— acetonitrile and then recording the optical spectrain 0.10 M KCl—H₂O, it was possible to observe optical transitionscharacteristic of polaron states in oxidized poly(pyrrole) (see FIG.3B). The polaron states have been reported to produce three opticaltransitions (26), which were observed at 2.0, 2.9, and 4.1 eV in FIG.3B. Upon reduction of the film (c.f. FIG. 3B), an increased intensityand a blue shift in the 2.9 eV band was observed, as expected for theπ→π* transition associated with the pyrrole units contained in thepolymer backbone (27).

[0048] As described in the experimental section, various plasticizerswere introduced into the polymer films (Table 3). TABLE 3 Plasticizersused in array elements* sensor plasticizer  1 none  2 none**  3poly(styrene)  4 poly(styrene)  5 poly(styrene)  6 poly(a-methylstyrene)  7 poly(styrene-acrylonitrile)  8 poly(styrene-maleic anydride) 9 poly(styrene-allyl alcohol) 10 poly(vinyl pyrrolidone) 11 poly(vinylphenol) 12 poly(vinyl butral) 13 poly(vinyl acetate) 14 poly(carbonate)

[0049] These inclusions allowed chemical control over the bindingproperties and electrical conductivity of the resulting plasticizedpolymers. Sensor arrays consisted of as many as 14 different elements,with each element synthesized to produce a distinct chemicalcomposition, and thus a distinct sensor response, for its polymer film.The resistance, R, of each film-coated individual sensor wasautomatically recorded before, during, and after exposure to variousodorants. A typical trial consisted of a 60 sec rest period in which thesensors were exposed to flowing air (3.0 liter-min⁻¹), a 60 sec exposureto a mixture of air (3.0 liter-min⁻¹) and air that had been saturatedwith solvent (0.5-3.5 liter-min⁻¹), and then a 240 sec exposure to air(3.0 liter-min⁻¹).

[0050] In an initial processing of the data, presented in this paper,the only information used was the maximum amplitude of the resistancechange divided by the initial resistance, ΔR_(max)/R_(i), of eachindividual sensor element. Most of the sensors exhibited eitherincreases or decreases in resistance upon exposure to different vapors,as expected from changes in the polymer properties upon exposure todifferent types chemicals (17-18). However, in some cases, sensorsdisplayed an initial decrease followed by an increase in resistance inresponse to a test odor. Since the resistance of each sensor couldincrease and/or decrease relative to its initial value, two values ofΔ_(max)/R_(i) were reported for each-sensor. The source of thebi-directional behavior of some sensor/odor pairs has not yet beenstudied in detail, but in most cases this behavior arose from thepresence of water (which by itself induced rapid decreases in the filmresistance) in the reagent-grade solvents used to generate the testodors of this study. The observed behavior in response to theseair-exposed, water-containing test solvents was reproducible andreversible on a given sensor array, and the environment wasrepresentative of many practical odor sensing applications in which airand water would not be readily excluded.

[0051] FIGS. 4B-D depicts representative examples of sensor amplituderesponses of a sensor array (see, Table 3). In this experiment, datawere recorded for 3 separate exposures to vapors of acetone, benzene,and ethanol flowing in air. The response patterns generated by thesensor array described in Table 3 are displayed for: (B) acetone; (C)benzene; and (D) ethanol. The sensor response was defined as the maximumpercent increase and decrease of the resistance divided by the initialresistance (gray bar and black bar respectively) of each sensor uponexposure to solvent vapor. In many cases sensors exhibited reproducibleincreases and decreases in resistance. An exposure consisted of: i) a 60sec rest period in which the sensors were exposed to flowing air (3.0liter-min⁻¹); ii) a 60 sec exposure to a mixture of air (3.0liter-min⁻¹) and air that had been saturated with solvent (0.5liter-min⁻¹); and iii) a 240 sec exposure to air (3.0 liter-min⁻¹). Itis readily apparent that these odorants each produced a distinctiveresponse on the sensor array. In additional experiments, a total of 8separate vapors (acetone, benzene, chloroform, ethanol, isopropylalcohol, methanol, tetrahydrofuran, and ethyl acetate), chosen to span arange of chemical and physical characteristics, were evaluated over a 5day period on a 14-element sensor array (Table 3). As discussed below,each odorant could be clearly and reproducibly identified from theothers using this sensor apparatus.

[0052] Principle component analysis (19) was used to simplifypresentation of the data and to quantify the distinguishing abilities ofindividual sensors and of the array as a whole. In this approach, linearcombinations of the Δ_(max)/R_(i) data for the elements in the arraywere constructed such that the maximum variance [defined as the squareof the standard deviation] was contained in the fewest mutuallyorthogonal dimensions. This allowed representation of most-of theinformation contained in data sets shown in FIGS. 4B-D in two (or three)dimensions. The resulting clustering, or lack thereof, of like exposuredata in the new dimensional space was used as a measure of thedistinguishing ability, and of the reproducibility, of the sensor array.

[0053] In order to illustrate the variation in sensor response ofindividual sensors that resulted from changes in the plasticizingpolymer, principle component analysis was performed on the individual,isolated responses of each of the 14 individual sensor elements in atypical array (FIG. 5). Data were obtained from multiple exposures toacetone (a), benzene (b), chloroform (c), ethanol (e), isopropyl alcohol(i), methanol (m), tetrahydrofuran (thf), or ethyl acetate (@) over aperiod of 5 days with the test vapors exposed to the array in varioussequences. The numbers of the figures refer to the sensor elementsdescribed in Table 3. The unites along the axes indicate the amplitudeof the principle component that was used to describe the particular dataset for an odor. The black regions indicate clusters corresponding to asingle solvent which could be distinguished from all others; grayregions highlight data of solvents whose signals overlapped with othersaround it. Exposure conditions were identical to those in FIG. 4.

[0054] Since each individual sensor produced two data values, principlecomponent analysis of these responses resulted in only two orthogonalprincipal components; pc1 and pc2. As an example of the selectivityexhibited by an individual sensor element, the sensor designated asnumber 5 in FIG. 5 (which was plasticized with poly(styrene)) confusedacetone with chloroform, isopropyl alcohol, and tetrahydrofuran. It alsoconfused benzene with ethyl acetate, while easily distinguishing ethanoland methanol from all other solvents. Changing the plasticizer to poly(α-methyl styrene) (sensor number 6 in FIG. 5) had little effect on thespatial distribution of the responses with respect to one another andwith respect to the origin. Thus, as expected, a rather slight chemicalmodification of the plasticizer had little effect on the relativevariance of the eight test odorants. In contrast, the addition of acyano group to the plasticizer, in the form ofpoly(styrene-acrylonitrile), (sensor number 7 in FIG. 5), resulted in alarger contribution to the overall variance by benzene and chloroform,while decreasing the contribution of ethanol. Changing the substituentgroup in the plasticizer to a hydrogen bonding acid (poly(styrene-allylalcohol), sensor number 9 in-FIG. 5) increased the contribution ofacetone to the overall variance while having little effect on the otherodors, with the exception of confusing methanol and ethanol. Theseresults suggest that the behavior of the sensors can be systematicallyaltered by varying the chemical composition of the plasticizing polymer.

[0055]FIG. 6 shows the principle component analysis for all 14 sensorsdescribed in Table 3 and FIGS. 4 and 5. When the solvents were projectedinto a three dimensional odor space (FIG. 6A or 6B), all eight solventswere easily distinguished with the specific array discussed herein.Detection of an individual test odor, based only on the criterion ofobserving ˜1% ΔR_(max)/R_(i) values for all elements in the array, wasreadily accomplished at the parts per thousand level with no controlover the temperature or humidity of the flowing air. Further increasesin sensitivity are likely after a thorough utilization of the temporalcomponents of the ΔR_(max)/R_(i) data as well as a more completecharacterization of the noise in the array.

[0056] We have also investigated the suitability of this sensor arrayfor identifying the components of certain test mixtures. This task isgreatly simplified if the array exhibits a predictable signal responseas the concentration of a given odorant is varied, and if the responsesof various individual odors are additive (i.e. if superposition ismaintained). When a 19-element sensor array was exposed to a number, n,of different acetone concentrations in air, the (CH₃)₂CO concentrationwas semi-quantitavely predicted from the first principle component. Thiswas evident from a good linear least square fit through the first threeprinciple components.

[0057] The same sensor array was also able to resolve the components invarious test methanol-ethanol mixtures (29). As shown in FIG. 7B, alinear relationship was observed between the first principle componentand the mole fraction of methanol in the liquid phase, x_(m), in aCH₃OH—C₂H₅OH mixture, demonstrating that superposition held for thismixture/sensor array combination. Furthermore, although the componentsin the mixture could be predicted fairly accurately from just the firstprinciple component, an increase in the accuracy could be achieved usinga multi-linear least square fit through the first three principlecomponents. This relationship held for CH₃OH/(CH₃OH+C₂H₅OH) ratios of 0to −1.0 in air-saturated solutions of this vapor mixture. The conductingpolymer-based sensor arrays could therefore not only distinguish betweenpure test vapors, but also allowed analysis of concentrations ofodorants as well as analysis of binary mixtures of vapors.

[0058] In summary, the results presented herein advance the area ofanalyte sensor design. A relatively simple array design, using only amultiplexed low-power dc electrical resistance readout signal, has beenshown to readily distinguish between various test odorants. Suchconducting polymer-based arrays are simple to construct and modify, andafford an opportunity to effect chemical control over the responsepattern of a vapor. For example, by increasing the ratio of plasticizerto conducting polymer, it is possible to approach the percolationthreshold, at which point the conductivity exhibits a very sensitiveresponse to the presence of the sorbed molecules. Furthermore, producingthinner films will afford the opportunity to obtain decreased responsetimes, and increasing the number of plasticizing polymers and polymerbackbone motifs will likely result in increased diversity among sensors.This type of polymer-based array is chemically flexible, is simple tofabricate, modify, and analyze, and utilizes a low power dc resistancereadout signal transduction path to convert chemical data intoelectrical signals. It provides a new approach to broadly-responsiveodor sensors for fundamental and applied investigations of chemicalmimics for the mammalian sense of smell. Such systems are useful forevaluating the generality of neural network algorithms developed tounderstand how the mammalian olfactory system identifies thedirectionality, concentration, and identity of various odors.

[0059] Fabrication and Testing of Carbon Black-Based Sensor Arrays.

[0060] Sensor Fabrication. Individual sensor elements were fabricated inthe following manner. Each non-conductive polymer (80 mg, see Table 4)was dissolved in 6 ml of THF. TABLE 4 Sensor # Non-Conductive Polymer  1poly(4-vinyl phenol)  2 poly(styrene - allyl alcohol)  3 poly(α-methylstyrene)  4 poly(vinyl chloride - vinyl acetate)  5 poly(vinyl acetate) 6 poly(N-vinyl pyrrolidone)  7 poly(bisphenol A carbonate)  8poly(styrene)  9 poly(styrene-maleic anhydride) 10 poly(sulfone)

[0061] Then, 20 mg of carbon black (BP 2000, Cabot Corp.) were suspendedwith vigorous mixing. Interdigitated electrodes (the cleaved capacitorspreviously described) were then dipped into this mixture and the solventallowed to evaporate. A series of such sensor elements with differingnon-conductive polymers were fabricated and incorporated into acommercial bus strip which allowed the chemiresistors to be easilymonitored with a multiplexing ohmmeter.

[0062] Sensor Array Testing. To evaluate the performance of thecarbon-black based sensors, arrays with as many as twenty elements wereexposed to a series of analytes. A sensor exposure consisted of (1) asixty second exposure to flowing air (6 liter min−1), (2) a sixty secondexposure to a mixture of air (6 liter min−1) and air that had beensaturated with the analyte (0.5 liter min−1), (3) a five minute recoveryperiod during which the sensor array was exposed to flowing air (6 litermin−1). The resistance of the elements were monitored during exposure,and depending on the thickness and chemical make-up of the film,resistance changes as large as 250% could be observed in response to ananalyte. In one experiment, a 10 element sensor array consistingcarbon-black composites formed with a series of non-conductive polymers(see Table 4) was exposed to acetone, benzene, chloroform, ethanol,hexane, methanol, and toluene over a two day period. A total of 58exposures to these analytes were performed in this time period. In allcases, resistance changes in response to the analytes were positive, andwith the exception of acetone, reversible (see FIG. 8). The maximumpositive-deviations were then subjected to principal component analysisin a manner analogous to that described for the poly(pyrrole) basedsensor. FIG. 9 shows the results of the principal component analysis forthe entire 10-element array. With the exception of overlap betweentoluene with benzene, the analytes were distinguished from one andother.

[0063] Cited References: 1. Lundström et al. (1991) Nature 352:47-50; 2.Shurmer and Gardner (1992) Sens. Act. B 8:1-11; 3. Reed (1992) Neuron8:205-209; 4. Lancet and Ben-Airie (1993). Curr. Biol. 3:668-674; 5.Kauer (1991) TINS 14:79-85; 6. DeVries and Baylor (1993) Cell10(S):139-149; 7. Gardner et al. (1991) Sens. Act. B 4:117-121; 8.Gardner et al. (1991) Sens. Act. B 6:71-75; 9. Corcoran et al. (1993)Sens. Act. B 15:32-37; 10. Grate and Abraham (1991) Sens. Act. B3:85-111; 11. Grate et al. (1993) Anal. Chem. 65:1868-1881; 12. Stetteret al. (1986) Anal. Chem. 58:860-866; 13. Stetter et al. (1990) Sens.Act. B 1:43-47; 14. Stetter et al. (1993) Anal. Chem. Acta 284:1-11; 15.Pearce et al. (1993) Analyst 118:371-377; 16, Shurmer et al. (1991)Sens. Act. B 4:29-33; 17. Topart and Josowicz (1992) J. Phys. Chem.96:7824-7830; 18. Charlesworth et al. (1993) J. Phys. Chem.97:5418-5423; 19. Hecht (1990) Mathematics in Chemistry: An Introductionto Modern Methods (Prentice Hall, Englewood Cliffs, N.J.); 20. Pope(1983) Heteropoly and Isopoly Oxometalates (Springer-Verlag, New York),chap. 4; 21. Salmon et al. (1982) J. Polym. Sci., Polym. Lett.20:187-193; 22. Andrieux et al. (1990) J. Am. Chem. Soc. 112:2439-2440;23. Diaz et al. (1981) J. Electroanal. Chem. 121:355-361; 24. Kanazawaet al. (1981) Synth. Met. 4:119-130; 25. Bidan et al. (1988) J.Electroanal. Chem. 251:297-306; 26. Kaufman et al. (1984) Phys. Rev.Lett. 53:1005-1008; 27. Yakushi et al. (1983) J. Chem. Phys.79:4774-4778; and 28. Morris et al. (1942) Can. J. Res. B 20:207-211.

[0064] All publications and patent applications cited in thisspecification are herein incorporated by reference as if each individualpublication or patent application were specifically and individuallyindicated to be incorporated by reference. Although the foregoinginvention has been described in some detail by way of illustration andexample for purposes of clarity of understanding, it will be readilyapparent to those of ordinary skill in the art in light of the teachingsof this invention that certain changes and modifications may be madethereto without departing from the spirit or scope of the appendedclaims.

What is claimed is:
 1. A sensor array for detecting an analyte in afluid for use in conjunction with an electrical measuring apparatus,said array comprising at least first and second chemical sensors eachcomprising: at least first and second conductive leads suitable forelectrical connection to the electrical measuring apparatus andelectrically coupled to a chemically sensitive resistor comprising aplurality of alternating nonconductive regions comprising anonconductive organic polymer and conductive regions comprising aconductive material compositionally different than said nonconductiveorganic polymer, said resistor providing an electrical path between saidconductive leads and through said regions, a first electrical resistancebetween said conductive leads when said resistor is contacted with afirst fluid comprising a chemical analyte at a first concentration, anda second electrical resistance between said conductive leads when saidresistor is contacted with a second fluid comprising said chemicalanalyte at a second different concentration, the difference between saidfirst electrical resistance and said second electrical resistance ofsaid first chemical sensor being different from the difference betweensaid first electrical resistance and said second electrical resistanceof said second chemical sensor.
 2. A sensor array according to claim 1,wherein said plurality of nonconductive regions of said first chemicalsensor is different from said plurality of nonconductive regions of saidsecond chemical sensor.
 3. A sensor array according to claim 1, whereinsaid nonconductive organic polymer of said first chemical sensor isqualitatively different from said nonconductive organic polymer of saidsecond chemical sensor.
 4. A sensor array according to claim 1, whereinsaid conductive material is an inorganic conductor.
 5. An system fordetecting an analyte in a fluid, said system comprising: at least firstand second chemical sensors each comprising at least first and secondconductive leads electrically coupled to a chemically sensitive resistorcomprising a plurality of alternating nonconductive regions comprising anonconductive organic polymer and conductive regions comprising aconductive material compositionally different than said nonconductiveorganic polymer, said resistor providing an electrical path between saidconductive leads and through said regions, a first electrical resistancebetween said conductive leads when said resistor is contacted with afirst fluid comprising a chemical analyte at a first concentration and asecond different electrical resistance when said resistor is contactedwith a second fluid comprising said chemical analyte at a seconddifferent concentration, the difference between said first electricalresistance and said second electrical resistance of said first chemicalsensor being different from the difference between said first electricalresistance and said second electrical resistance of said second chemicalsensor; an electrical measuring device electrically connected to atleast one of said conductive leads; and a computer comprisng a residentalgorithm; said electrical measuring device being capable of detectingsaid first and said second electrical resistances in each said sensorand said computer capable of assembling said resistances into a sensorarray response profile.
 6. A system according to claim 5, wherein saidplurality of nonconductive regions of said first chemical sensor isdifferent from said plurality of nonconductive regions of said secondchemical sensor.
 7. A system according to claim 5, wherein saidnonconductive organic polymer of said first chemical sensor isqualitatively different from said nonconductive organic polymer of saidsecond chemical sensor.
 8. A system according to claim 5, wherein saidconductive material is an inorganic conductor.
 9. A method for detectingthe presence of an analyte in a fluid, said method comprising:resistively sensing the presence of an analyte in a fluid with achemical sensor comprising first and second conductive leadselectrically coupled to a chemically sensitive resistor comprising aplurality of alternating nonconductive regions comprising anonconductive organic polymer and conductive regions comprising aconductive material compositionally different than said nonconductiveorganic polymer, said resistor providing an electrical path between saidconductive leads and through said regions, a first resistance betweensaid conductive elements when said resistor is contacted with a firstfluid comprising a chemical analyte at a first concentration and asecond different resistance when said resistor is contacted with asecond fluid comprising said chemical analyte at a second differentconcentration.
 10. A method according to claim 9, wherein said pluralityof nonconductive regions of said first chemical sensor is different fromsaid plurality of nonconductive regions of said second chemical sensor.11. A method according to claim 9, wherein said nonconductive organicpolymer of said first chemical sensor is qualitatively different fromsaid nonconductive organic polymer of said second chemical sensor.
 12. Amethod according to claim 9, wherein said conductive material is aninorganic conductor.
 13. A method according to claim 9, said first andsaid resistance each being a resistance over time.